CN1884275A - Ethoxyl quercetin derivative, method for preparation and use - Google Patents
Ethoxyl quercetin derivative, method for preparation and use Download PDFInfo
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- CN1884275A CN1884275A CNA2006100452930A CN200610045293A CN1884275A CN 1884275 A CN1884275 A CN 1884275A CN A2006100452930 A CNA2006100452930 A CN A2006100452930A CN 200610045293 A CN200610045293 A CN 200610045293A CN 1884275 A CN1884275 A CN 1884275A
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- quercetin
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Abstract
The invention relates to hydroxyethylated meletin derivative with general formula (I), and the R1, R2, R3, R4, R5 are H or -CH2CH2OH, and at least one of R1, R2, R3, R4, R5 is -CH2CH2OH, but R1, R2 are not H, and R3, R4, R5 are -CH2CH2OH. The invention also relates to method for preparing said compound, comprising dissolving meletin in basic solution, adding epoxyethane or chlorethanol, stirring, neutralizing with acid to be neutral, getting coarse product; removing salt with one methodof normal chromatogram, chromatogram, hyperfiltration, ion exchange, electrodialysis and hyperfiltration; drying and getting yellow or amber-yellow powder hydroxyethylated meletin derivative. The product is widely used in preparing drug, cosmetics, health products and foodstuff.
Description
Technical field
The present invention relates to a kind of quercetin derivative and preparation method thereof and application, relate in particular to four ethoxyl quercetin derivatives and preparation method thereof and preparing medicine, makeup, healthcare products, Application in Food.
Background technology
Quercetin more extensively is present in the natural drug, has the effect of antitumor action, anti-allergic effects, antioxygenation, platelet aggregation-against, and, obtain more and more paying attention to and using.But, because Quercetin is water insoluble, make Quercetin very inconvenient when being applied to the field of medicine, makeup, healthcare products, food, also be restricted sometimes.Therefore, develop quercetin derivative soluble in water and become the urgent at present problem that solves with the field that is conveniently used in medicine, makeup, healthcare products, food with same pharmic function.
Chinese patent application numbers 200410062585.6, the document of publication number CN1715277A discloses a kind of the prepare compound for the treatment of cardiovascular and cerebrovascular diseases and preparation method thereof and its application at pharmacy field, the derivative TriHEQ that wherein relates to Quercetin can be used for treatment or prevention cardiovascular and cerebrovascular diseases or prevention of brain palsy.
But other derivatives of Quercetin, particularly four ethoxyl quercetin derivatives and preparation thereof yet there are no report.
Summary of the invention
Deficiency in existing Quercetin and derivative technology of preparing and the application the purpose of this invention is to provide a kind of quercetin derivative soluble in water---ethoxyl quercetin derivative and preparation method thereof and application.
The ethoxyl quercetin derivative that the present invention relates to is represented with following general formula (1):
Wherein:
R
1Be H or-CH
2CH
2OH;
R
2Be H or-CH
2CH
2OH;
R
3Be H or-CH
2CH
2OH;
R
4Be H or-CH
2CH
2OH;
R
5Be H or-CH
2CH
2OH;
And R
1, R
2, R
3, R
4, R
5In have at least one to be-CH
2CH
2OH, but do not comprise R
1, R
2Be H, R
3, R
1, R
5Be-CH
2CH
2OH.
Above-mentioned compound, preferably: R
1, R
1, R
1, R
5In have at least one to be-CH
2CH
2OH.
Above-mentioned compound most preferably is: R
2Be H; R
1, R
3, R
4, R
5Be-CH
2CH
2OH.
The preparation method of above-claimed cpd, be made up of following steps:
(1) to be dissolved in 0.1～20 part of weight pH value be in 7.1～14 the basic solution to 1 part of weight of Quercetin;
(2) oxyethane or the chloroethanol of 0.1～30 part of weight of adding, stirring reaction 0.5-46 hour;
(3) be neutralized to neutrality with acid, get thick product solution;
(4) adopting one of conventional crystallization, chromatogram, extraction, ion-exchange, electrodialysis or reverse osmosis method to remove desalts;
(5) spray-dried or conventional concentrated, vacuum-drying gets yellow or faint yellow powdery ethoxyl quercetin derivative.
In the preparation method of above-claimed cpd: the alkali in the described basic solution of step (1) is NaOH, KOH, Na preferably
2CO
3, K
2CO
3, the alkali of one of NaH, Na, pyridine or its several mixtures arbitrarily with the mixed alkali of arbitrary proportion.
In the preparation method of above-claimed cpd: the solvent of the described basic solution of step (1) preferably water, methyl alcohol, ethanol, pyridine, one of DMF (N, dinethylformamide), DMSO (dimethyl sulfoxide (DMSO)) or its is several with the mixed mixture of arbitrary proportion arbitrarily.
Wherein, the solvent in the described basic solution of step (1) most preferably is one of water, DMF, DMSO.
In the preparation method of above-claimed cpd: the add-on of described oxyethane of step (2) or chloroethanol is 5-25 part weight preferably; And the weight ratio of oxyethane or chloroethanol and Quercetin is 0.1～1.6: 1.
Wherein, the preferred 6-38 hour described stirring reaction time of step (2).
In the preparation method of above-claimed cpd: the described acid of step (3) is one of hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, formic acid, acetic acid preferably.
In the preparation method of above-claimed cpd: the described chromatographic column of step (4) is one of silica gel chromatography, gel chromatography, polymeric amide chromatogram, reverse silica gel chromatography preferably;
Wherein, the preferred extraction agent of the described extraction of step (4) is the mixture of acetone, propyl carbinol, Virahol, ethyl acetate, chloroform, methylene dichloride, one or more arbitrary proportions of ether;
Wherein, preferably weakly acidic cation-exchange resin and strongly basic anion exchange resin are got in the described ion-exchange of step (4);
Wherein, the described electrodialysis of step (4) is anode membrane preferably: sulfonic group cation exchange resin membrane, cavity block: amido anion-exchange resin membrane;
Above-claimed cpd is in preparation medicine, makeup, healthcare products, Application in Food.
The ethoxyl quercetin derivative that utilizes method of the present invention to obtain is soluble in water, can be applicable to medicine, makeup, healthcare products, field of food, has the prospect of marketing widely.
The preparation method of the ethoxyl quercetin derivative that the present invention relates to is easy, practical, productive rate is high, cost is low, and is easy to realize suitability for industrialized production.
Embodiment
Embodiment 1
In the flask of 500mL, add 4.0gNaOH, 250mL water, stirring and dissolving.Add the 60g Quercetin afterwards, stir and make it whole dissolvings.Under agitation drip 32mL oxyethane, continue reaction 30 hours under the air tight condition again.Hydrochloric acid neutralization reaction liquid with 2mol/L is extremely neutral, and the spent ion exchange resin desalination, and concentrated through decompression heating (70 ℃) again, spraying drying get 58.6g four ethoxyl quercetins.
Products obtained therefrom is carried out chemical structure with mass spectrum and nucleus magnetic resonance to be identified.
Product appearance is the pale yellow powder shape, and hydrochloric acid-magnesium powder reaction is positive, and is shown as flavonoid compound.
Mass spectrum (FAB-MS): m/z 478.2[M]
+, 434.1 (four ethoxyl quercetins lose a fragment behind the hydroxyethyl).
Nucleus magnetic resonance
17CNMR (75MHz, DMSO-d
6), δ ppm:146.7 (C-2), 136.7 (C-3), 176.2 (C-4), 160.4 (C-5), 98.0 (C-6), 164.6 (C-7), 92.7 (C-8), 156.3 (C-9), 104.1 (C-10), 123.4 (C-1 '), (113.2 C-2 '), 148.1 (C-3 '), 150.4 (C-4 '), (113.2 C-5 '), 122.0 (C-6 '), 70.8,70.7,70.5,70.4 (OCH
2* 4), 58.8,58.6,58.5,58.4 (CH
2-* 4).
1HNMR(300MHz，DMSO-d
6)：12.41(s，1H，OH-5)，7.82(d，1H，H-6′)，7.81(s，1H，H-2′)，7.16(d，1H，H-5′)，7.15(s，1H，H-8)，6.33(s，1H，H-6)，4.08(m，8H，-OCH
2×4)，3.89(m，8H，-CH
2-×4)。
Embodiment 2
In the flask of 250mL, add 1.4gNaH, 200mL DMF, stirring and dissolving.Add the 30g Quercetin afterwards, be stirred to dissolving.Under agitation drip the 20mL chloroethanol, continue reaction 24 hours again.With the sulfuric acid neutralization reaction liquid of 1mol/L to neutral, through concentrating under reduced pressure, and with the gel chromatographic columns desalination, take off DMF, vacuum (20kPa) drying must the 26.3g ethoxyl quercetin derivative.
Embodiment 3
In the flask of 250mL, add 10.2g KOH, 100mL water, stirring and dissolving.Add the 15g Quercetin afterwards, be stirred to dissolving.Under agitation drip 3mL oxyethane, continue reaction 22 hours under the air tight condition again.To neutral, remove water through n-butanol extraction with the acetic acid neutralization reaction liquid of 2mol/L, propyl carbinol is reclaimed in the propyl carbinol heating (being lower than 80 ℃) of reducing pressure mutually, again through vacuum-drying, gets the 13.2g ethoxyl quercetin derivative.
Embodiment 4
In the flask of 250mL, add 0.5gK
2CO
3, 50mL pyridine, stirring and dissolving.Add the 7.6g Quercetin afterwards, be stirred to dissolving.Under agitation drip the 2.2mL chloroethanol, continue reaction 38 hours again.Phosphoric acid neutralization reaction liquid with 1mol/L is extremely neutral, and through electrodialytic desalting, spraying drying after decompression heating (70 ℃) concentrates can get the 3.2g ethoxyl quercetin derivative.
Embodiment 5
In the flask of 100mL, add 0.5g Na
2CO
3, 30mL water, stirring and dissolving.Add the 3.8g Quercetin afterwards, be stirred to dissolving.Under agitation drip 0.8mL oxyethane, continue reaction 46 hours under the air tight condition again.Hydrochloric acid neutralization reaction liquid with 1mol/L is extremely neutral, and concentrating under reduced pressure steams about 15 mL, and cold filtration falls sodium-chlor, and mother liquor is concentrating under reduced pressure again, and crystallisation by cooling is separated out product, filters after vacuum-drying can get the 1.3g ethoxyl quercetin derivative.
Embodiment 6
In the flask of 100mL, add 1.2gNaH, 40mL DMSO, stirring and dissolving.Add the 3.5g Quercetin afterwards, be stirred to dissolving.Under agitation drip 1.8mL oxyethane, continue reaction 2 hours under the air tight condition again.With the sulfuric acid neutralization reaction liquid of 1mol/L to neutral, through concentrating under reduced pressure, and with the silica gel chromatographic column desalination, take off DMSO, vacuum (20kPa) drying can get the 2.8g ethoxyl quercetin derivative.
Embodiment 7
In the flask of 100mL, add 2.0gNaOH, 40mL water, stirring and dissolving.Add the 3.2g Quercetin afterwards, stir and make it whole dissolvings.Under agitation drip 2.1mL oxyethane, continue reaction 30 hours under the air tight condition again.Hydrochloric acid neutralization reaction liquid with 2mol/L is extremely neutral, and through ethyl acetate extraction, organic phase reclaims ethyl acetate, through vacuum-drying, gets the 2.6g ethoxyl quercetin derivative.
Claims (9)
1. the compound of following general formula (1):
Wherein:
R
1Be H or-CH
2CH
2OH;
R
2Be H or-CH
2CH
2OH;
R
3Be H or-CH
2CH
2OH;
R
4Be H or-CH
2CH
2OH;
R
5Be H or-CH
2CH
2OH;
And R
1, R
2, R
3, R
4, R
5In have at least one to be-CH
2CH
2OH, but do not comprise R
1, R
2Be H, R
3, R
4, R
5Be-CH
2CH
2OH.
2. according to the described compound of claim 1, it is characterized in that: R
1, R
3, R
4, R
5In have at least one to be-CH
2CH
2OH.
3. according to the described compound of claim 2, it is characterized in that: R
2Be H; R
1, R
3, R
4, R
5Be-CH
2CH
2OH.
4. the preparation method of the described compound of one of claim 1～3, be made up of following steps:
(1) to be dissolved in 0.1～20 part of weight pH value be in 7.1～14 the basic solution to 1 part of weight of Quercetin;
(2) oxyethane or the chloroethanol of 0.1～30 part of weight of adding, stirring reaction 0.5-46 hour;
(3) be neutralized to neutrality with acid, get thick product solution;
(4) adopting one of conventional crystallization, chromatogram, extraction, ion-exchange, electrodialysis or reverse osmosis method to remove desalts;
(5) spray-dried or conventional concentrated, vacuum-drying gets yellow or faint yellow powdery ethoxyl quercetin derivative.
5. as the preparation method of compound as described in the claim 4, it is characterized in that: the alkali in the described basic solution of step (1) is NaOH, KOH, Na
2CO
3, K
2CO
3, the alkali of one of NaH, Na, pyridine or its several mixtures arbitrarily with the mixed alkali of arbitrary proportion.
6. as the preparation method of compound as described in the claim 4, it is characterized in that: the solvent of the described basic solution of step (1) is that water, methyl alcohol, ethanol, pyridine, one of DMF (N, dinethylformamide), DMSO (dimethyl sulfoxide (DMSO)) or its are several with the mixed mixture of arbitrary proportion arbitrarily.
7. as the preparation method of compound as described in the claim 4, it is characterized in that: the add-on of described oxyethane of step (2) or chloroethanol is 5-25 part weight; And the weight ratio of oxyethane or chloroethanol and Quercetin is 0.1～1.6: 1.
8. the preparation method of compound as claimed in claim 4, it is characterized in that: the described acid of step (3) is one of hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, formic acid, acetic acid.
9. the described compound of one of claim 1～3 is in preparation medicine, makeup, healthcare products, Application in Food.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100452930A CN1884275A (en) | 2006-07-07 | 2006-07-07 | Ethoxyl quercetin derivative, method for preparation and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100452930A CN1884275A (en) | 2006-07-07 | 2006-07-07 | Ethoxyl quercetin derivative, method for preparation and use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1884275A true CN1884275A (en) | 2006-12-27 |
Family
ID=37582592
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006100452930A Pending CN1884275A (en) | 2006-07-07 | 2006-07-07 | Ethoxyl quercetin derivative, method for preparation and use |
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| Country | Link |
|---|---|
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101220064B (en) * | 2008-01-24 | 2012-10-17 | 沈阳药科大学 | Novel scutellaria glycosides compounds and uses thereof |
| CN101723768B (en) * | 2009-12-18 | 2013-12-25 | 贵州省中国科学院天然产物化学重点实验室 | Method for carrying out hydroxyethylation on phenolic acid compounds and products thereof |
| CN106854223A (en) * | 2017-01-05 | 2017-06-16 | 石家庄学院 | Mustargen quercetin derivative and its production and use |
| WO2020033498A1 (en) * | 2018-08-10 | 2020-02-13 | Whitehead Institute For Biomedical Research | Analogs of the natural product icariin |
| US10639294B2 (en) | 2018-10-02 | 2020-05-05 | Janssen Pharmaceutica Nv | Pharmaceutical compositions comprising a hydroxyethylquercetin glucuronide metabolite |
| US11304968B2 (en) | 2018-11-16 | 2022-04-19 | Janssen Pharmaceutica Nv | Pharmaceutical compositions comprising a hydroxyethylquercetin glucuronide |
-
2006
- 2006-07-07 CN CNA2006100452930A patent/CN1884275A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101220064B (en) * | 2008-01-24 | 2012-10-17 | 沈阳药科大学 | Novel scutellaria glycosides compounds and uses thereof |
| CN101723768B (en) * | 2009-12-18 | 2013-12-25 | 贵州省中国科学院天然产物化学重点实验室 | Method for carrying out hydroxyethylation on phenolic acid compounds and products thereof |
| CN106854223A (en) * | 2017-01-05 | 2017-06-16 | 石家庄学院 | Mustargen quercetin derivative and its production and use |
| CN106854223B (en) * | 2017-01-05 | 2019-03-29 | 石家庄学院 | Mustargen quercetin derivative and its preparation method and application |
| WO2020033498A1 (en) * | 2018-08-10 | 2020-02-13 | Whitehead Institute For Biomedical Research | Analogs of the natural product icariin |
| US11377466B2 (en) | 2018-08-10 | 2022-07-05 | Whitehead Institute For Biomedical Research | Analogs of the natural product icariin |
| US10639294B2 (en) | 2018-10-02 | 2020-05-05 | Janssen Pharmaceutica Nv | Pharmaceutical compositions comprising a hydroxyethylquercetin glucuronide metabolite |
| US11304968B2 (en) | 2018-11-16 | 2022-04-19 | Janssen Pharmaceutica Nv | Pharmaceutical compositions comprising a hydroxyethylquercetin glucuronide |
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